The candidate is a MD., Ph.D. with training in mammalian genetics pursuing post-doctoral work in the laboratory of Jane Gitschier concurrent with training at UCSF as a Clinical Molecular Genetics Fellow. UCSF is an excellent research environment with diverse scientific resources available to the candidate. His long term research goals are to establish an independent research laboratory focused on mammalian metal metabolism. His clinical goals are in the field of molecular diagnostics of genetic diseases. His long term goal is to establish a clinical molecular genetics laboratory devoted to the diagnosis of these rare disorders. Genetic approaches to the identification of mammalian genes involved in metal metabolism and characterization of the corresponding proteins will be the primary focus of this proposal. There are two specific aims in this research proposal: 1) Identify the intestinal iron exporter by positional cloning of the gene affected in sla (sex linked anemia). Sla, a mouse mutant with defective iron export, provides the means to identify a key component in the poorly understood process of iron transit through the intestine. The location of sla gene will be refined with an inter-specific cross, ancestral chromosome mapping, and exclusion mapping and a physical map of sla region will be constructed. Functional complementation of the sla defect with large insert clones in transgenic mice will be used to further refine the sla region. Candidate genes will be identified by standard means and evaluated for a role in sla. 2) Characterize a novel ceruloplasmin homologue expressed in the brain and determine its role in iron and copper metabolism. The complete cDNA will identified and sequenced and the chromosomal location of the gene determined. Study of temporal and spatial mRNA expression pattern and a homologous knockout will help define its functional role.